EP3413033B1 - Method and apparatus for determining properties of a laboratory sample contained in a laboratory sample container - Google Patents

Method and apparatus for determining properties of a laboratory sample contained in a laboratory sample container Download PDF

Info

Publication number
EP3413033B1
EP3413033B1 EP17175373.4A EP17175373A EP3413033B1 EP 3413033 B1 EP3413033 B1 EP 3413033B1 EP 17175373 A EP17175373 A EP 17175373A EP 3413033 B1 EP3413033 B1 EP 3413033B1
Authority
EP
European Patent Office
Prior art keywords
laboratory sample
sample container
light
properties
laboratory
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP17175373.4A
Other languages
German (de)
French (fr)
Other versions
EP3413033A1 (en
Inventor
Michael Rein
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
F Hoffmann La Roche AG
Roche Diagnostics GmbH
Original Assignee
F Hoffmann La Roche AG
Roche Diagnostics GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by F Hoffmann La Roche AG, Roche Diagnostics GmbH filed Critical F Hoffmann La Roche AG
Priority to EP17175373.4A priority Critical patent/EP3413033B1/en
Priority to JP2018100390A priority patent/JP6749964B2/en
Priority to US15/996,898 priority patent/US11009499B2/en
Priority to CN201810586121.7A priority patent/CN109030425A/en
Publication of EP3413033A1 publication Critical patent/EP3413033A1/en
Application granted granted Critical
Publication of EP3413033B1 publication Critical patent/EP3413033B1/en
Priority to US17/231,065 priority patent/US20210231641A1/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/49—Blood
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/59—Transmissivity
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/49—Blood
    • G01N33/491—Blood by separating the blood components
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/06—Investigating concentration of particle suspensions
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1429—Signal processing
    • G01N15/1433—Signal processing using image recognition
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1434—Optical arrangements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/01—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials specially adapted for biological cells, e.g. blood cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/06—Investigating concentration of particle suspensions
    • G01N15/075—Investigating concentration of particle suspensions by optical means
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N2015/0092—Monitoring flocculation or agglomeration
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N2015/1006—Investigating individual particles for cytology
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N2021/178—Methods for obtaining spatial resolution of the property being measured
    • G01N2021/1785—Three dimensional
    • G01N2021/1787—Tomographic, i.e. computerised reconstruction from projective measurements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/84—Systems specially adapted for particular applications
    • G01N21/88—Investigating the presence of flaws or contamination
    • G01N21/94—Investigating contamination, e.g. dust
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/06—Illumination; Optics
    • G01N2201/066—Modifiable path; multiple paths in one sample
    • G01N2201/0662—Comparing measurements on two or more paths in one sample

Definitions

  • the invention relates to a method and an apparatus for determining properties of a laboratory sample contained in a laboratory sample container.
  • sample containers comprising centrifuged blood samples may have to be processed.
  • the blood samples may be separated into serum and cruor (blood cells) by a separating medium. If e.g. an aliquot of the serum has to be generated, part of the serum has to be transferred to another sample container, e.g. by means of a pipette device. If impurities, e.g. in form of foreign matter, are present in the serum, the pipette device may not function properly, since the impurities may block or close an opening of the pipette device.
  • EP 2 770 318 A1 discloses a method for detecting clots in serum, the serum being comprised in a laboratory sample container.
  • labels comprising sample related information are placed on the laboratory sample container. These labels complicate the process of optically detecting properties of the laboratory sample.
  • WO 2016/020684 A1 discloses a method for determining properties of a laboratory sample contained in a laboratory sample container, wherein the method comprises the steps: measuring projections of the laboratory sample container comprising the laboratory sample by irradiating light to the laboratory sample container at different projection angles, and determining the properties by tomographic reconstruction based on the projections.
  • the method for determining properties of a laboratory sample contained in a laboratory sample container is based on a tomographic measurement process including tomographic reconstruction.
  • a tomographic measurement process including tomographic reconstruction Regarding the fundamentals of the tomographic measurement process including tomographic reconstruction reference is made to the relevant technical literature, e.g. to https://en.wikipedia.org/wiki/Tomographic_reconstruction
  • the method comprises the step of measuring projections of the laboratory sample container comprising the laboratory sample by irradiating light to the laboratory sample container at different projection angles.
  • a projection of an object here an object in form of the laboratory sample container comprising the laboratory sample, results from the tomographic measurement process at a given projection angle.
  • the projection is typically made up of a set of line integrals.
  • the projections may be represented by a vector, wherein elements of the vector are formed by the line integrals e.g. in a binary representation.
  • An intensity of light irradiated to the laboratory sample container is chosen such that a sufficient quantity of light passes through the laboratory sample container, even if a label is placed on the laboratory sample container.
  • a wavelength of the light may e.g. be chosen in the visible or infrared wavelength range.
  • the method further comprises the step of determining the properties by tomographic reconstruction based on the projections.
  • the properties may e.g. be embodied as a cross sectional image of the laboratory sample container and of the laboratory sample.
  • the image may e.g. be formed by discrete pixels.
  • the properties of the sample may be reliably determined, even if labels are placed on the laboratory sample container. Further, a cross sectional image of the laboratory sample may be obtained making it possible to detect impurities in the laboratory sample.
  • the above described method steps may be repeated for a number of different vertical positions in order to obtain a number of cross sectional images of the laboratory sample container and of the laboratory sample at the different vertical positions.
  • the step of measuring the projections comprises the steps: irradiating light to the laboratory sample container, such that the light passes through the laboratory sample container and the laboratory sample, and measuring an intensity of light exiting the laboratory sample container, wherein the light exiting the laboratory sample container is based on the irradiated light.
  • light is irradiated to the laboratory sample container in form of parallel light rays or beams at the respective projection angles.
  • the parallel light rays or beams may be located in a horizontal projection plane being perpendicular to an axis of the laboratory sample container. Accordingly, the light exiting the laboratory sample container may be measured in the projection plane.
  • the projections made under the different projection angles form a sinogram. Reference is made insofar also to the relevant technical literature.
  • the tomographic reconstruction is based on the Radon Transformation, and/or a Fourier-Domain Reconstruction Algorithm, and/or a Filtered Back Projection Algorithm, and/or an Iterative Reconstruction Algorithm, and/or Fan-Beam Reconstruction, and/or spiral computed tomography.
  • a Fourier-Domain Reconstruction Algorithm and/or a Filtered Back Projection Algorithm, and/or an Iterative Reconstruction Algorithm, and/or Fan-Beam Reconstruction, and/or spiral computed tomography.
  • the properties of the laboratory sample are the light attenuation coefficients of the laboratory sample as a function of a position or location inside the laboratory sample container.
  • the laboratory sample is a centrifuged blood sample, the blood sample being separated into serum and at least one other component.
  • the at least one other component may e.g. embodied as cruor (blood cells), a separating medium (gel) or air.
  • foreign matter in the serum may be detected based on the determined properties.
  • the foreign matter may e.g. be embodied as a clot typically consisting of afibrinogenaemia fibers, coagulum, fat/protein agglutination or the like.
  • properties of labels attached to the laboratory sample container may be determined based on the determined properties.
  • the properties of labels may e.g. be if a label is placed on the laboratory sample container, an extension of the label placed on the laboratory sample container, a thickness of the label and/or a number of layers of the label.
  • the laboratory sample is classified based on the determined properties.
  • Typical classes which can be assigned to a laboratory sample e.g. in form of a blood plasma sample, are, for example, a lipemic class, a hemolytic class, an icteric class and a good class.
  • the "good" class contains those samples which are not assigned to the class lipemic, hemolytic or icteric.
  • the sample is to be assigned to the lipemic class, it is a lipemic sample which has an elevated level of lipids. This may, for example, be an indication of a disorder of the fat metabolism.
  • the hemolytic class it is a hemolytic sample which has an elevated level of hemoglobin.
  • This may, for example, be an indication of particular anemias, transfusion reactions or malaria.
  • the blood plasma sample is to be assigned to the icteric class, it is an icteric sample which has an elevated level of bilirubin. This may, for example, be an indication of a disease of the liver.
  • the apparatus for determining properties of a laboratory sample contained in a laboratory sample container is adapted to perform the method as described above.
  • a liquid level of the laboratory sample comprised in the laboratory sample container is determined based on the determined properties.
  • a rough cell analysis is performed based on the determined properties.
  • the apparatus e.g. forming a laboratory diagnostic device, comprises a light source for irradiating light to the laboratory sample container, such that the light passes through the laboratory sample container and the laboratory sample.
  • the light source may e.g. be embodied as a number (e.g. 10 to 100) of linearly arranged laser diodes irradiating light in form of parallel rays at the respective projection angles.
  • the laser diodes may be linearly arranged in a horizontal projection plane being perpendicular to an axis of the laboratory sample container.
  • the apparatus further comprises a light detector for measuring an intensity of light being based on the irradiated light and exiting the laboratory sample container.
  • the light detector may e.g. be embodied as a number (e.g. 10 to 100) of linearly arranged photo detectors.
  • the photo detectors may be linearly arranged in the horizontal projection plane horizontally spaced from the laser diodes, such that the sample container can be placed between the laser diodes and the photo detector.
  • the apparatus further comprises a rotating drive for rotating the light source together with the light detector relative to the sample container to cause different projection angles.
  • the apparatus further comprises a numeric processor for determining the properties by tomographic reconstruction based on the projections.
  • Fig. 1 schematically depicts an apparatus 10 for determining properties of a laboratory sample 1 contained in a laboratory sample container 2.
  • the properties of the laboratory sample 1 are the light attenuation coefficients of the laboratory sample 1 in a projection plane.
  • the laboratory sample 1 is a centrifuged blood sample.
  • the blood sample 1 is separated into cruor 4, serum 3 and air 5.
  • the blood sample 1 contains foreign matter 6 in the serum 3 in form of a clot. Further, a label 7 comprising sample related information is attached to the laboratory sample container 2.
  • the apparatus 10 comprises a light source 11 in form of a linear array of a number n of laser diodes 11a for irradiating light to the laboratory sample container 2, such that the light passes through the laboratory sample container 2 and the laboratory sample 1 in form of parallel rays R1 to Rn.
  • the apparatus 10 further comprises a light detector 12 for determining projections forming a sinogram by measuring an intensity of light exiting the laboratory sample container 2 and being based on the irradiated light.
  • the light detector 12 is formed by a linear array of n photo detectors 12a, e.g. in form of photo diodes.
  • the number n of laser diodes 11a and photo detectors 12a, respectively, may e.g. lie in the range between 4 and 100.
  • the laser diodes 11a and the photo detectors 12a are placed oppositely to one another in a common projection plane.
  • the sample container 2 is placed between the laser diodes 11a and the photo detectors 12a.
  • the projection plane is perpendicular to an axis of the sample container 2.
  • the apparatus 10 further comprises a rotating drive 13 for rotating the light source 11 and the light detector 12 relative to the sample container 2 to effect different projection angles ⁇ 1 and ⁇ 2, see fig. 2 .
  • the apparatus 10 further comprises a processor 14 for determining the properties by tomographic reconstruction based on the projections P1 and P2.
  • the apparatus 10 operates as follows.
  • the laser diodes 11a By means of the laser diodes 11a light in form parallel light beams or rays R1 to Rn is irradiated to the laboratory sample container 2 at a first projection angle ⁇ 1, such that the light passes through the laboratory sample container 2 and the laboratory sample 1.
  • the photo detectors 12a By means of the photo detectors 12a an intensity of light being based on the irradiated light and exiting the laboratory sample container 2 is measured.
  • a projection P1 is formed by the different measured values of the photo detectors 12a.
  • the rotating drive 13 rotates the light source 11 and the light detector 12 relative to the sample container 2 to effect the projection angle ⁇ 2 and the above steps are repeated to generate the projection P2.
  • the processor 14 determines the properties by tomographic reconstruction based on the projections P1 and P2.
  • the tomographic reconstruction may be based on the Radon Transformation, and/or a Fourier-Domain Reconstruction Algorithm, and/or a Filtered Back Projection Algorithm, and/or an Iterative Reconstruction Algorithm, and/or Fan-Beam Reconstruction and/or spiral computed tomography.
  • the properties of the laboratory sample 1 in form of the light attenuation coefficients of the laboratory sample 1 in the projection plane are evaluated.
  • the properties may be represented in form of a digital image being composed of pixels representing the corresponding light attenuation coefficients in the projection plane.
  • the extent of the clot 6 in the projection plane for all measured vertical levels may be determined, even if a label 7 is placed on the laboratory sample container 2.
  • the pixel resolution typically depends on the number n of laser diodes 11a and photo detectors 12a.
  • laboratory sample 1 may be classified based on the light attenuation coefficients, since the light attenuation coefficients are e.g. specific for lipemic, hemolytic class, an icteric samples.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Pathology (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • General Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Dispersion Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Ecology (AREA)
  • Biophysics (AREA)
  • Signal Processing (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Investigating Materials By The Use Of Optical Means Adapted For Particular Applications (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Computer Vision & Pattern Recognition (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Description

  • The invention relates to a method and an apparatus for determining properties of a laboratory sample contained in a laboratory sample container.
  • In the technical field of laboratory automation laboratory sample containers comprising centrifuged blood samples may have to be processed. The blood samples may be separated into serum and cruor (blood cells) by a separating medium. If e.g. an aliquot of the serum has to be generated, part of the serum has to be transferred to another sample container, e.g. by means of a pipette device. If impurities, e.g. in form of foreign matter, are present in the serum, the pipette device may not function properly, since the impurities may block or close an opening of the pipette device.
  • EP 2 770 318 A1 discloses a method for detecting clots in serum, the serum being comprised in a laboratory sample container.
  • Typically, labels comprising sample related information are placed on the laboratory sample container. These labels complicate the process of optically detecting properties of the laboratory sample.
  • WO 2016/020684 A1 discloses a method for determining properties of a laboratory sample contained in a laboratory sample container, wherein the method comprises the steps: measuring projections of the laboratory sample container comprising the laboratory sample by irradiating light to the laboratory sample container at different projection angles, and determining the properties by tomographic reconstruction based on the projections.
  • It is an object of the invention to provide a method and an apparatus for determining properties of a laboratory sample contained in a laboratory sample container providing reliable results in determining the properties, even if labels are placed on the laboratory sample container.
  • This object is solved by a method according to claim 1 and an apparatus according to claim 11.
  • The method for determining properties of a laboratory sample contained in a laboratory sample container is based on a tomographic measurement process including tomographic reconstruction. Regarding the fundamentals of the tomographic measurement process including tomographic reconstruction reference is made to the relevant technical literature, e.g. to https://en.wikipedia.org/wiki/Tomographic_reconstruction
  • The method comprises the step of measuring projections of the laboratory sample container comprising the laboratory sample by irradiating light to the laboratory sample container at different projection angles. A projection of an object, here an object in form of the laboratory sample container comprising the laboratory sample, results from the tomographic measurement process at a given projection angle. The projection is typically made up of a set of line integrals. The projections may be represented by a vector, wherein elements of the vector are formed by the line integrals e.g. in a binary representation.
  • An intensity of light irradiated to the laboratory sample container is chosen such that a sufficient quantity of light passes through the laboratory sample container, even if a label is placed on the laboratory sample container. A wavelength of the light may e.g. be chosen in the visible or infrared wavelength range.
  • The method further comprises the step of determining the properties by tomographic reconstruction based on the projections. The properties may e.g. be embodied as a cross sectional image of the laboratory sample container and of the laboratory sample. The image may e.g. be formed by discrete pixels.
  • Due to the inventive method, the properties of the sample may be reliably determined, even if labels are placed on the laboratory sample container. Further, a cross sectional image of the laboratory sample may be obtained making it possible to detect impurities in the laboratory sample.
  • The above described method steps may be repeated for a number of different vertical positions in order to obtain a number of cross sectional images of the laboratory sample container and of the laboratory sample at the different vertical positions.
  • According to an embodiment, the step of measuring the projections comprises the steps: irradiating light to the laboratory sample container, such that the light passes through the laboratory sample container and the laboratory sample, and measuring an intensity of light exiting the laboratory sample container, wherein the light exiting the laboratory sample container is based on the irradiated light.
  • According to an embodiment, light is irradiated to the laboratory sample container in form of parallel light rays or beams at the respective projection angles. The parallel light rays or beams may be located in a horizontal projection plane being perpendicular to an axis of the laboratory sample container. Accordingly, the light exiting the laboratory sample container may be measured in the projection plane.
  • According to an embodiment, the projections made under the different projection angles form a sinogram. Reference is made insofar also to the relevant technical literature.
  • According to an embodiment, the tomographic reconstruction is based on the Radon Transformation, and/or a Fourier-Domain Reconstruction Algorithm, and/or a Filtered Back Projection Algorithm, and/or an Iterative Reconstruction Algorithm, and/or Fan-Beam Reconstruction, and/or spiral computed tomography. Reference is made insofar to the relevant technical literature.
  • The properties of the laboratory sample are the light attenuation coefficients of the laboratory sample as a function of a position or location inside the laboratory sample container.
  • According to an embodiment, the laboratory sample is a centrifuged blood sample, the blood sample being separated into serum and at least one other component. The at least one other component may e.g. embodied as cruor (blood cells), a separating medium (gel) or air.
  • According to an embodiment, foreign matter in the serum may be detected based on the determined properties. The foreign matter may e.g. be embodied as a clot typically consisting of afibrinogenaemia fibers, coagulum, fat/protein agglutination or the like.
  • According to an embodiment, properties of labels attached to the laboratory sample container may be determined based on the determined properties. The properties of labels may e.g. be if a label is placed on the laboratory sample container, an extension of the label placed on the laboratory sample container, a thickness of the label and/or a number of layers of the label.
  • According to an embodiment, the laboratory sample is classified based on the determined properties. Typical classes which can be assigned to a laboratory sample, e.g. in form of a blood plasma sample, are, for example, a lipemic class, a hemolytic class, an icteric class and a good class. The "good" class contains those samples which are not assigned to the class lipemic, hemolytic or icteric. When the sample is to be assigned to the lipemic class, it is a lipemic sample which has an elevated level of lipids. This may, for example, be an indication of a disorder of the fat metabolism. When the sample is to be assigned to the hemolytic class, it is a hemolytic sample which has an elevated level of hemoglobin. This may, for example, be an indication of particular anemias, transfusion reactions or malaria. When the blood plasma sample is to be assigned to the icteric class, it is an icteric sample which has an elevated level of bilirubin. This may, for example, be an indication of a disease of the liver.
  • The apparatus for determining properties of a laboratory sample contained in a laboratory sample container is adapted to perform the method as described above.
  • According to an embodiment, a liquid level of the laboratory sample comprised in the laboratory sample container is determined based on the determined properties.
  • According to an embodiment, a rough cell analysis is performed based on the determined properties.
  • The apparatus, e.g. forming a laboratory diagnostic device, comprises a light source for irradiating light to the laboratory sample container, such that the light passes through the laboratory sample container and the laboratory sample. The light source may e.g. be embodied as a number (e.g. 10 to 100) of linearly arranged laser diodes irradiating light in form of parallel rays at the respective projection angles. The laser diodes may be linearly arranged in a horizontal projection plane being perpendicular to an axis of the laboratory sample container.
  • The apparatus further comprises a light detector for measuring an intensity of light being based on the irradiated light and exiting the laboratory sample container. The light detector may e.g. be embodied as a number (e.g. 10 to 100) of linearly arranged photo detectors. The photo detectors may be linearly arranged in the horizontal projection plane horizontally spaced from the laser diodes, such that the sample container can be placed between the laser diodes and the photo detector.
  • The apparatus further comprises a rotating drive for rotating the light source together with the light detector relative to the sample container to cause different projection angles.
  • The apparatus further comprises a numeric processor for determining the properties by tomographic reconstruction based on the projections.
  • The invention will now be described in detail with respect to the attached drawings, wherein
    • Fig. 1
    schematically depicts an apparatus for determining properties of a laboratory sample contained in a laboratory sample container in a perspective view, and
    Fig. 2
    schematically depicts the apparatus of Fig. 1 in a top view in two different projection angles.
  • Fig. 1 schematically depicts an apparatus 10 for determining properties of a laboratory sample 1 contained in a laboratory sample container 2. The properties of the laboratory sample 1 are the light attenuation coefficients of the laboratory sample 1 in a projection plane.
  • The laboratory sample 1 is a centrifuged blood sample. The blood sample 1 is separated into cruor 4, serum 3 and air 5. The blood sample 1 contains foreign matter 6 in the serum 3 in form of a clot. Further, a label 7 comprising sample related information is attached to the laboratory sample container 2.
  • The apparatus 10 comprises a light source 11 in form of a linear array of a number n of laser diodes 11a for irradiating light to the laboratory sample container 2, such that the light passes through the laboratory sample container 2 and the laboratory sample 1 in form of parallel rays R1 to Rn.
  • The apparatus 10 further comprises a light detector 12 for determining projections forming a sinogram by measuring an intensity of light exiting the laboratory sample container 2 and being based on the irradiated light. The light detector 12 is formed by a linear array of n photo detectors 12a, e.g. in form of photo diodes.
  • The number n of laser diodes 11a and photo detectors 12a, respectively, may e.g. lie in the range between 4 and 100.
  • The laser diodes 11a and the photo detectors 12a are placed oppositely to one another in a common projection plane. The sample container 2 is placed between the laser diodes 11a and the photo detectors 12a. The projection plane is perpendicular to an axis of the sample container 2.
  • The apparatus 10 further comprises a rotating drive 13 for rotating the light source 11 and the light detector 12 relative to the sample container 2 to effect different projection angles α1 and α2, see fig. 2.
  • The apparatus 10 further comprises a processor 14 for determining the properties by tomographic reconstruction based on the projections P1 and P2.
  • Now also referring to fig. 2, the apparatus 10 operates as follows.
  • By means of the laser diodes 11a light in form parallel light beams or rays R1 to Rn is irradiated to the laboratory sample container 2 at a first projection angle α1, such that the light passes through the laboratory sample container 2 and the laboratory sample 1. By means of the photo detectors 12a an intensity of light being based on the irradiated light and exiting the laboratory sample container 2 is measured. A projection P1 is formed by the different measured values of the photo detectors 12a.
  • If the projection P1 is generated, the rotating drive 13 rotates the light source 11 and the light detector 12 relative to the sample container 2 to effect the projection angle α2 and the above steps are repeated to generate the projection P2.
  • Self-evidently, typically more than the two exemplarily depicted projections P1 and P2 at the respective projection angles α1 and α2 are used to determine the properties. E.g., a number of 15 to 180 projections covering an angle range of 180 angular degrees may be used to determine the properties.
  • If the projections are determined, the processor 14 determines the properties by tomographic reconstruction based on the projections P1 and P2. The tomographic reconstruction may be based on the Radon Transformation, and/or a Fourier-Domain Reconstruction Algorithm, and/or a Filtered Back Projection Algorithm, and/or an Iterative Reconstruction Algorithm, and/or Fan-Beam Reconstruction and/or spiral computed tomography.
  • The above described steps are then repeated for different vertical levels, e.g. covering the complete vertical extension of the serum 3.
  • By means of the inventive apparatus and method, the properties of the laboratory sample 1 in form of the light attenuation coefficients of the laboratory sample 1 in the projection plane are evaluated. The properties may be represented in form of a digital image being composed of pixels representing the corresponding light attenuation coefficients in the projection plane. Thus, the extent of the clot 6 in the projection plane for all measured vertical levels may be determined, even if a label 7 is placed on the laboratory sample container 2.
  • The pixel resolution typically depends on the number n of laser diodes 11a and photo detectors 12a.
  • Further, the laboratory sample 1 may be classified based on the light attenuation coefficients, since the light attenuation coefficients are e.g. specific for lipemic, hemolytic class, an icteric samples.

Claims (11)

  1. Method for determining properties of a laboratory sample (1) contained in a laboratory sample container (2), wherein the method comprises the steps:
    - measuring projections (P1, P2) of the laboratory sample container (2) comprising the laboratory sample (1) by irradiating light to the laboratory sample container (2) at different projection angles (α1, α2), and
    - determining the properties of the laboratory sample (1) by tomographic reconstruction based on the projections (P1, P2),
    characterized in that
    - the properties of the laboratory sample (1) are the light attenuation coefficients of the laboratory sample (1) as a function of its position inside the laboratory sample container (2).
  2. Method according to claim 1, characterized in that
    - the step of measuring the projections (P1, P2) comprises the steps:
    - irradiating light to the laboratory sample container (2), such that the light passes through the laboratory sample container (2) and the laboratory sample (1), and
    - measuring an intensity of light being based on the irradiated light and exiting the laboratory sample container (2).
  3. Method according to claim 1 or 2, characterized in that
    - light is irradiated to the laboratory sample container (2) in form of parallel rays (R1 to Rn) at the respective projection angles (α1, α2).
  4. Method according to one of the preceding claims, characterized in that
    - the projections (P1, P2) form a sinogram.
  5. Method according to one of the preceding claims, characterized in that
    - the tomographic reconstruction is based on the Radon Transformation, and/or a Fourier-Domain Reconstruction Algorithm, and/or a Filtered Back Projection Algorithm, and/or an Iterative Reconstruction Algorithm, and/or Fan-Beam Reconstruction and/or spiral computed tomography.
  6. Method according to one of the preceding claims, characterized in that
    - the laboratory sample (1) is a centrifuged blood sample, the blood sample being separated into serum (3) and at least one other component (4, 5).
  7. Method according to claim 6, characterized by the step
    - detecting foreign matter (6) in the serum (3) based on the determined properties.
  8. Method according to one of the preceding claims, characterized by the step
    - determining properties of labels (7) attached to the laboratory sample container (2) based on the determined properties.
  9. Method according to one of the preceding claims, characterized in that
    - the laboratory sample (1) is classified based on the determined properties.
  10. Method according to one of the preceding claims, characterized in that
    - a liquid level of the laboratory sample (1) comprised in the laboratory sample container (2) is determined based on the determined properties.
  11. Apparatus (10) for determining properties of a laboratory sample (1) contained in a laboratory sample container (2), wherein the apparatus (10) is adapted to perform the method of one of the preceding claims, the apparatus (10) comprising:
    - a light source (11) for irradiating light to the laboratory sample container (2), such that the light passes through the laboratory sample container (2) and the laboratory sample (1),
    - a light detector (12) for determining projections (P1, P2) by measuring an intensity of light being based on the irradiated light and exiting the laboratory sample container (2),
    - a rotating drive (13) for rotating the light source (11) and the light detector (12) relative to the sample container (2) to effect different projection angles (α1, α2), and
    - a processor (14) for determining the properties of the laboratory sample (1) by tomographic reconstruction based on the projections (P1, P2),
    characterized in that
    - the properties of the laboratory sample (1) are the light attenuation coefficients of the laboratory sample (1) as a function of its position inside the laboratory sample container (2).
EP17175373.4A 2017-06-09 2017-06-09 Method and apparatus for determining properties of a laboratory sample contained in a laboratory sample container Active EP3413033B1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP17175373.4A EP3413033B1 (en) 2017-06-09 2017-06-09 Method and apparatus for determining properties of a laboratory sample contained in a laboratory sample container
JP2018100390A JP6749964B2 (en) 2017-06-09 2018-05-25 Method and apparatus for determining the properties of an experimental sample contained in an experimental sample container
US15/996,898 US11009499B2 (en) 2017-06-09 2018-06-04 Method and apparatus for determining properties of a laboratory sample contained in a laboratory sample container by tomographic reconstruction
CN201810586121.7A CN109030425A (en) 2017-06-09 2018-06-08 Method and apparatus for determining the property for the laboratory sample being contained in laboratory sample container
US17/231,065 US20210231641A1 (en) 2017-06-09 2021-04-15 Method and apparatus for determining properties of a laboratory sample contained in a laboratory sample container

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP17175373.4A EP3413033B1 (en) 2017-06-09 2017-06-09 Method and apparatus for determining properties of a laboratory sample contained in a laboratory sample container

Publications (2)

Publication Number Publication Date
EP3413033A1 EP3413033A1 (en) 2018-12-12
EP3413033B1 true EP3413033B1 (en) 2020-09-23

Family

ID=59054001

Family Applications (1)

Application Number Title Priority Date Filing Date
EP17175373.4A Active EP3413033B1 (en) 2017-06-09 2017-06-09 Method and apparatus for determining properties of a laboratory sample contained in a laboratory sample container

Country Status (4)

Country Link
US (2) US11009499B2 (en)
EP (1) EP3413033B1 (en)
JP (1) JP6749964B2 (en)
CN (1) CN109030425A (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3748414A1 (en) * 2019-06-07 2020-12-09 Koninklijke Philips N.V. A simple and efficient biopsy scanner with improved z-axis resolution

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4580219A (en) * 1983-05-02 1986-04-01 General Electric Company Method for reducing image artifacts due to projection measurement inconsistencies
US5447159A (en) * 1993-02-03 1995-09-05 Massachusetts Institute Of Technology Optical imaging for specimens having dispersive properties
US6636623B2 (en) 2001-08-10 2003-10-21 Visiongate, Inc. Optical projection imaging system and method for automatically detecting cells with molecular marker compartmentalization associated with malignancy and disease
US7738945B2 (en) * 2002-04-19 2010-06-15 University Of Washington Method and apparatus for pseudo-projection formation for optical tomography
US7197355B2 (en) * 2002-04-19 2007-03-27 Visiongate, Inc. Variable-motion optical tomography of small objects
US7978887B2 (en) * 2003-06-17 2011-07-12 Brown University Methods and apparatus for identifying subject matter in view data
US7560699B2 (en) * 2004-02-25 2009-07-14 Digirad Corporation Small field-of-view detector head (“SPECT”) attenuation correction system
JP4472442B2 (en) * 2004-06-24 2010-06-02 アロカ株式会社 Interface detection device, volume measuring device, and interface detection method
DE602006005843D1 (en) * 2005-11-23 2009-04-30 Koninkl Philips Electronics Nv DEVICE FOR ILLUMINATING THE INSIDE OF A TRUE MEDIUM
CN102132149B (en) * 2008-06-27 2014-05-28 沃尔弗拉姆·R·雅里施 High efficiency computed tomography
US8284892B2 (en) * 2008-12-22 2012-10-09 General Electric Company System and method for image reconstruction
US8155420B2 (en) * 2009-05-21 2012-04-10 Visiongate, Inc System and method for detecting poor quality in 3D reconstructions
US20120307962A1 (en) * 2009-12-16 2012-12-06 Georgia Tech Resarch Corporation Systems and methods for x-ray fluorescence computed tomography imaging with nanoparticles
CN101726460B (en) * 2009-12-17 2012-05-30 浙江大学 Device and method for detecting distribution image of each substance in fluid
JP5220060B2 (en) * 2010-06-02 2013-06-26 株式会社アドバンテスト Electromagnetic wave measuring apparatus, measuring method, program, recording medium
US8215046B2 (en) * 2010-07-20 2012-07-10 Advanced Technology International USA, LLC Forend with multiple locator rails
DE102010063412B4 (en) * 2010-12-17 2013-06-06 Laser Zentrum Hannover E.V. Technique for tomographic image acquisition
US9521982B2 (en) * 2011-06-17 2016-12-20 The Board Of Trustees Of The Leland Stanford Junior University Computed tomography system with dynamic bowtie filter
US9451926B2 (en) * 2012-05-09 2016-09-27 University Of Washington Through Its Center For Commercialization Respiratory motion correction with internal-external motion correlation, and associated systems and methods
WO2014124057A1 (en) * 2013-02-05 2014-08-14 Massachusetts Institute Of Technology 3-d holographic imaging flow cytometry
EP2770318B1 (en) 2013-02-21 2018-03-21 Roche Diagniostics GmbH Method and apparatus for detecting clots in a liquid and laboratory automation system
WO2014168567A1 (en) * 2013-04-11 2014-10-16 Flatfrog Laboratories Ab Tomographic processing for touch detection
JP6143584B2 (en) * 2013-07-04 2017-06-07 株式会社日立ハイテクノロジーズ Detector and biological sample analyzer
US10285659B2 (en) * 2013-12-06 2019-05-14 Rensselaer Polytechnic Institute Stored luminescence computed tomography
GB201413872D0 (en) * 2014-08-05 2014-09-17 Imp Innovations Ltd Multiplexed optical projection tomography
DE102014113433B4 (en) * 2014-09-17 2016-07-14 Carl Zeiss Ag Device and method for three-dimensional imaging of an object
US10437038B2 (en) * 2015-02-20 2019-10-08 Max-Planck-Geselleschaft Zur Foerderung Der Wissenschaften E.V. Device and method for creating an optical tomogram of a microscopic sample
US10537299B2 (en) * 2015-06-04 2020-01-21 Rensselaer Polytechnic Institute Attenuation map reconstruction from TOF PET data
JP2017086172A (en) * 2015-11-02 2017-05-25 キヤノン株式会社 Subject information acquisition device and control method thereof
US10607378B2 (en) * 2016-11-18 2020-03-31 Wolfram R. JARISCH Extended high efficiency computed tomography with optimized recursions and applications
WO2018160998A1 (en) * 2017-03-02 2018-09-07 Arizona Board Of Regents On Behalf Of Arizona State University Live-cell computed tomography

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Also Published As

Publication number Publication date
US20180356392A1 (en) 2018-12-13
CN109030425A (en) 2018-12-18
EP3413033A1 (en) 2018-12-12
JP6749964B2 (en) 2020-09-02
US20210231641A1 (en) 2021-07-29
JP2019002915A (en) 2019-01-10
US11009499B2 (en) 2021-05-18

Similar Documents

Publication Publication Date Title
JP6005683B2 (en) Method and apparatus for determining interfering substances and physical dimensions in liquid samples and containers analyzed by a clinical analyzer
JP6879366B2 (en) Methods, devices and quality check modules for detecting hemolysis, jaundice, lipemia, or normality of a sample
JP6927465B2 (en) Model-based methods and equipment for classifying interfering factors in specimens
EP3149492B1 (en) Methods and systems for tube inspection and liquid level detection
JP7055818B2 (en) HILIN evaluation method and device using convolutional neural network
JP5997256B2 (en) Measurement of cell volume and components
JP5734838B2 (en) Method for measuring the area of a sample placed in an analysis chamber
US7688448B2 (en) Through-container optical evaluation system
US10068322B2 (en) Inspection system
HU220571B1 (en) Method and device for fault checking of reservoirs filled with fluid
US10311569B1 (en) Identifying liquid blood components from sensed data to monitor specimen integrity
EP3413033B1 (en) Method and apparatus for determining properties of a laboratory sample contained in a laboratory sample container
US10545163B1 (en) Sample extraction and rotation device for automated blood sample processing systems
US11125763B1 (en) Specimen integrity monitoring device for automated blood sample processing systems
KR102000938B1 (en) Method for Setting Inspection Criteria Automatically by Indicating Regions and Smart Learning Method for X-ray Inspection Using the Same
JP6218352B2 (en) Display device, display method and display program used in measurement system
JP2002181702A (en) Specimen inspection device
WO2024052440A1 (en) Inspection system and method for a closed medical container

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN PUBLISHED

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20190603

RBV Designated contracting states (corrected)

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: EXAMINATION IS IN PROGRESS

RIC1 Information provided on ipc code assigned before grant

Ipc: G01N 35/04 20060101ALN20190809BHEP

Ipc: G01N 15/06 20060101ALN20190809BHEP

Ipc: G01N 15/04 20060101ALN20190809BHEP

Ipc: G01N 33/49 20060101ALI20190809BHEP

Ipc: G01N 15/14 20060101ALI20190809BHEP

Ipc: G01N 15/10 20060101ALN20190809BHEP

Ipc: G01N 21/94 20060101ALN20190809BHEP

Ipc: G01N 21/17 20060101ALI20190809BHEP

Ipc: G01N 21/51 20060101AFI20190809BHEP

17Q First examination report despatched

Effective date: 20190918

RIC1 Information provided on ipc code assigned before grant

Ipc: G01N 15/14 20060101ALI20190913BHEP

Ipc: G01N 21/51 20060101AFI20190913BHEP

Ipc: G01N 21/94 20060101ALN20190913BHEP

Ipc: G01N 15/06 20060101ALN20190913BHEP

Ipc: G01N 21/17 20060101ALI20190913BHEP

Ipc: G01N 15/04 20060101ALN20190913BHEP

Ipc: G01N 35/04 20060101ALN20190913BHEP

Ipc: G01N 33/49 20060101ALI20190913BHEP

Ipc: G01N 15/10 20060101ALN20190913BHEP

RIC1 Information provided on ipc code assigned before grant

Ipc: G01N 15/06 20060101ALN20200205BHEP

Ipc: G01N 33/49 20060101ALI20200205BHEP

Ipc: G01N 35/04 20060101ALN20200205BHEP

Ipc: G01N 15/04 20060101ALN20200205BHEP

Ipc: G01N 15/10 20060101ALN20200205BHEP

Ipc: G01N 15/14 20060101ALI20200205BHEP

Ipc: G01N 21/51 20060101AFI20200205BHEP

Ipc: G01N 21/94 20060101ALN20200205BHEP

Ipc: G01N 21/17 20060101ALI20200205BHEP

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: GRANT OF PATENT IS INTENDED

RIC1 Information provided on ipc code assigned before grant

Ipc: G01N 15/04 20060101ALN20200317BHEP

Ipc: G01N 35/04 20060101ALN20200317BHEP

Ipc: G01N 33/49 20060101ALI20200317BHEP

Ipc: G01N 21/51 20060101AFI20200317BHEP

Ipc: G01N 21/94 20060101ALN20200317BHEP

Ipc: G01N 21/17 20060101ALI20200317BHEP

Ipc: G01N 15/06 20060101ALN20200317BHEP

Ipc: G01N 15/14 20060101ALI20200317BHEP

Ipc: G01N 15/10 20060101ALN20200317BHEP

INTG Intention to grant announced

Effective date: 20200408

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE PATENT HAS BEEN GRANTED

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602017023994

Country of ref document: DE

Ref country code: AT

Ref legal event code: REF

Ref document number: 1316896

Country of ref document: AT

Kind code of ref document: T

Effective date: 20201015

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201223

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201223

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201224

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 1316896

Country of ref document: AT

Kind code of ref document: T

Effective date: 20200923

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: RS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

REG Reference to a national code

Ref country code: NL

Ref legal event code: MP

Effective date: 20200923

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG4D

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: SM

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210125

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: AL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210123

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602017023994

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

26N No opposition filed

Effective date: 20210624

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

REG Reference to a national code

Ref country code: BE

Ref legal event code: MM

Effective date: 20210630

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20210609

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20210609

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20210630

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: IT

Payment date: 20220615

Year of fee payment: 6

Ref country code: GB

Payment date: 20220526

Year of fee payment: 6

Ref country code: FR

Payment date: 20220517

Year of fee payment: 6

Ref country code: DE

Payment date: 20220512

Year of fee payment: 6

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CH

Payment date: 20220702

Year of fee payment: 6

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: NL

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20200923

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO

Effective date: 20170609

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 602017023994

Country of ref document: DE

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20230609

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20200923

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20240103

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20230630

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20230609